CN112041675B

CN112041675B - Methods and multiple analyte titration systems for colorimetric end-point detection

Info

Publication number: CN112041675B
Application number: CN201980028900.8A
Authority: CN
Inventors: P·R·克劳斯; J·W·博尔达克; R·J·赖瑟
Original assignee: Ecolab USA Inc
Current assignee: Ecolab USA Inc
Priority date: 2018-04-09
Filing date: 2019-04-09
Publication date: 2023-06-09
Anticipated expiration: 2039-04-09
Also published as: WO2019199730A1; CA3096538A1; EP3775874A1; AU2019253603A1; BR112020020717B1; US20190310235A1; US11454619B2; CN112041675A; BR112020020717A2

Abstract

A system for quantifying the concentration of one or more target analytes in a treatment solution is provided and may be used, for example, in a method of quantifying the concentration of a target analyte. These systems and methods include continuous and batch auto-titration methods that use chemical titration to measure the target analyte concentration in the process solution using a multi-wavelength detector. The method provides an effective and practical auto-titration method for multiple target analytes, and may include methods of analyzing more than one analyte and providing a dynamic range for measuring the concentration of more than one target analyte.

Description

Methods and multiple analyte titration systems for colorimetric end-point detection

Technical Field

A system for quantifying the concentration of one or more target analytes in a treatment solution is provided and may be used, for example, in a method of quantifying the concentration of a target analyte. These systems and methods include continuous auto-titration methods that use chemical titration to measure target analyte concentrations in a process solution. The method provides an effective and practical auto-titration method for multiple target analytes, and may include methods of analyzing more than one analyte and providing a dynamic range for measuring the concentration of more than one target analyte.

Background

Titration is a well known and practiced method for determining the concentration of a component of a solution. Various chemical titrations are practiced, wherein a titrant is typically added to a solution in which it reacts with its selected component. Once all of the reaction components have reacted with the known titrant, a measurable or significant change occurs, indicating that the reaction is complete. In some cases, the apparent change comprises a color change. For example, color changes can vary widely between various chemical titrations.

Although titration is known to be a science, it can be a cumbersome process requiring careful practice by a chemist or other skilled operator. In some cases, it may be impractical for a chemist or other technician to manually perform the titration, although it may be desirable to obtain data obtained by titration. An automatic titrator may be used that attempts to determine when a complete reaction has occurred and to perform appropriate titration calculations to determine the amount of a component in solution. However, depending on the reaction, it may be difficult for an automated process to accurately determine the reaction endpoint. In addition, automated systems may require a significant amount of time to complete a process, which may be undesirable or unacceptable if the solution needs to be monitored at specific time intervals.

Disclosure of Invention

An automatic titration system is provided, comprising: a reaction manifold for mixing a continuous flow and updated sample stream containing unknown concentrations of one or more analytes with a titrant; a sample pump for pumping the continuous flow and renewed sample stream into the reaction manifold; a first titrant pump for pumping the first titrant into the reaction manifold to contact the continuous flow and the renewed sample stream; a multi-wavelength detector for detecting a first titration endpoint of a reaction between the analyte and the first titrant; and a controller communicatively coupled with the sample pump, the first titrant pump, and the detector, wherein the controller controls the sample pump to set the flow rate of the continuous flow and the updated sample flow, controls the first titrant pump to set the flow rate of the first titrant, and receives data from the detector to detect the first titration endpoint of the reaction between the analyte and the first titrant, and determines the analyte concentration at the first titration endpoint.

An automatic titration system is provided, comprising: a reaction manifold for mixing a sample stream containing an unknown concentration of an analyte with a first titrant; a sample pump for pumping the sample stream into the reaction manifold; a first titrant pump for pumping the first titrant into the reaction manifold to contact the sample stream; a multi-wavelength detector for detecting a first titration endpoint of a reaction between the analyte and the first titrant; and a controller communicatively coupled with the sample pump, the first titrant pump, and the detector, wherein the controller controls the sample pump to set a flow rate of the sample stream, controls the first titrant pump to set a flow rate of the first titrant, and receives data from the detector to detect the first titration endpoint of the reaction between the analyte and the first titrant, and determines an analyte concentration at the first titration endpoint.

The auto-titration system described herein may cause the sample stream to contain two or more analytes.

Additionally, the auto-titration system described herein may further comprise a second titrant pump for pumping a second titrant into the reaction manifold to contact the batch sample flow or the continuous flow and updated sample flow. The multi-wavelength detector may further detect a second titration endpoint of the reaction between the analyte and the second titrant, the controller further communicatively coupled to the second titrant pump, and the controller further controls the second titrant pump to set a flow rate of the second titrant, and receives data from the detector to detect the second titration endpoint of the reaction between the analyte and the second titrant, and determine an analyte concentration at the second titration endpoint.

The automatic titration system described herein may react the second titrant with a second analyte.

The auto-titration system described herein may further comprise a third titrant pump for pumping a third titrant into the reaction manifold to contact the batch sample flow or the continuous flow and updated sample flow. The multi-wavelength detector may further detect a third titration endpoint of the reaction between the analyte and the third titrant, the controller further communicatively coupled to the third titrant pump, and the controller further controls the third titrant pump to set a flow rate of the third titrant, and receives data from the detector to detect the third titration endpoint of the reaction between the analyte and the third titrant, and determine an analyte concentration at the third titration endpoint.

The automatic titration system described herein may react the third titrant with a third analyte.

The auto-titration system described herein may enable the multi-wavelength detector to detect signals in the ultraviolet to visible range.

Also, the auto-titration system described herein may make the multi-wavelength detector a spectrometer.

The auto-titration system described herein may have the reaction manifold contain a liquid mixer downstream of the titrant inlet and upstream of the detector.

The auto-titration system described herein may further comprise a conditioning manifold upstream of the titrant inlet and downstream of the sample flow inlet.

The auto-titration system described herein may have the conditioning manifold comprise a liquid mixer.

The auto-titration system described herein may further include a mixing circuit with the conditioning manifold.

The auto-titration system described herein may further comprise a conditioning reagent pump for pumping conditioning reagent into the conditioning manifold to mix with the continuous flow and the renewed sample stream.

The automatic titration system may make the adjusting reagent be a pH buffer, a reaction catalyst, a chemical indicator, a chelating agent, a surfactant, a conductivity-altering salt, an ion-pairing reagent, a biochemical substance, or a combination thereof.

The auto-titration system described herein may include the conditioning reagent comprising potassium iodide, sulfuric acid, acetic acid, a starch indicator, ammonium molybdate, or a combination thereof.

The automatic titration system can cause the conditioning reagent pump to further comprise a first conditioning reagent pump for pumping a first conditioning reagent and a second conditioning reagent pump for pumping a second conditioning reagent.

The automatic titration system can cause the first conditioning reagent to be a metal iodide and the second conditioning reagent to be an indicator.

The auto-titration system described herein can cause the conditioning reagent pump to inject the conditioning reagent into a flowing sample stream, wherein the controller is communicatively coupled to the conditioning reagent pump and configured to control the conditioning reagent pump to set a flow rate of the conditioning reagent injected into the batch sample stream or the continuous flow and updated sample stream.

The auto-titration system described herein may be used in a method of quantifying an analyte of interest.

For example, described herein is a method for quantifying a concentration of a target analyte in a sample stream, comprising: continuously flowing and continuously updating the sample stream at a known flow rate through an analyzer comprising a manifold and a multi-wavelength detector; quantifying the target analyte concentration by continuously adding a titrant to the analyzer, and by changing the titrant concentration by increasing or decreasing the flow rate of the titrant within a specified range to set a titrant concentration change; and detecting a titration endpoint of a reaction between the target analyte and the titrant in the sample stream over a specified target analyte concentration range.

Furthermore, a method for quantifying a target analyte concentration in a sample stream may comprise: adding the sample to an analyzer comprising a manifold and a multi-wavelength detector; quantifying the target analyte concentration by adding a titrant to the analyzer, and by changing the titrant concentration by increasing or decreasing the flow rate of the titrant within a specified range to set a titrant concentration change; and detecting a titration endpoint of a reaction between the target analyte and the titrant in the sample stream over a specified target analyte concentration range; wherein the sample stream comprises two or more analytes.

The quantification method may be such that the sample stream comprises two or more analytes.

The method may further comprise the sample stream with a second analyte.

The methods described herein may further comprise quantifying the second analyte by continuously adding a second titrant to the batch sample stream or the continuous flow and continuous update sample stream.

The method may further comprise the sample stream with a third analyte.

The quantification method may further comprise quantifying the third analyte by continuously adding a third titrant to the batch sample stream or the continuous flow and continuous update sample stream.

The method may provide a known flow rate of the sample of about 1 μl/min to about 200 mL/min.

The method may provide a known flow rate of the sample of about 5 mL/min to about 25 mL/min.

The method may further comprise continuously adding a conditioning reagent to the sample stream at a concentration proportional to the target analyte concentration.

The quantification method may further comprise detecting the titration endpoint using a multi-wavelength detector at a defined distance from a titrant addition point, and calculating the titrant concentration using the distance between the detector and the titrant addition point, the flow rate of the titrant, and the system volume.

The methods described herein may further comprise varying the concentration of the titrant by controlling its flow rate, wherein the detector signal from the titrated reaction product is correlated in time with the titrant concentration.

The method may further comprise administering a known concentration of calibrator into the sample stream, detecting the concentration of calibrator, and calculating a response.

The method of quantifying may further comprise controlling the titrant concentration using a feedback loop responsive to a detector detecting a reaction between the titrant and the target analyte.

The method described herein, wherein the modulating reagent treats the sample stream to improve detection of the target analyte.

The method may improve detection of the target analyte by improving the sensitivity of the detection method.

The methods described herein can make the conditioning agent a pH buffer, a reaction catalyst, a chemical indicator, a chelating agent, a surfactant, a conductivity altering salt, an ion pair agent, a biochemical, or a combination thereof.

The quantification method may include the modulating agent comprising potassium iodide, acetic acid, a starch indicator, or a combination thereof.

The methods described herein can increase or decrease the flow rate of the continuous flow and continuously updated sample stream depending on whether the titration endpoint can be detected within the specified target analyte concentration range.

Drawings

FIG. 1 is a schematic diagram of an auto-titration system with two analytes in a sample and two titrant pumps, four conditioning reagent pumps and one multi-wavelength detector in the system.

FIG. 2 is a schematic diagram of an auto-titration system with three analytes in a sample and three titrant pumps, three conditioning reagent pumps and one multi-wavelength detector in the system.

FIG. 3A is a graph of absorbance versus wavelength for a titration of caustic with a 0.1N hydrochloric acid solution.

FIG. 3B is a graph of absorbance versus droplet count for a titration of caustic with a 0.1N hydrochloric acid solution.

Fig. 4A shows the spectra at each of the test concentrations of 6-40ppm on a peracid sample at approximately 15 ppm.

Fig. 4B is a graph of absorbance versus wavelength calculated from the spectrum shown in fig. 4A.

Fig. 5 is a graph of absorbance versus concentration and shows the same trend of absorbance versus concentration curve.

Fig. 6 is a graph of absorbance versus wavelength showing that the detector provides similar results as the standard.

Fig. 7A is a graph of the titrimetric absorbance versus wavelength for a laboratory 17 grain (grin) water titration using the hardness test kit # 307. Fig. 7B shows the number of droplets required for the same titration.

Detailed Description

The auto-titration systems and methods described herein have been developed to provide for analysis of more than one analyte. An advantage of these systems and methods is the detection of an endpoint using a multi-wavelength detector that allows for the detection of a titration endpoint in the visible wavelength range. The use of a spectrometer and a broad spectrum light source enables the titrator detector system to select the optimal wavelength required for the intended titration application. The optimal wavelength can be selected by absorbance scanning of the desired molecule (e.g., starch-iodine complex). Typically, the wavelength with the greatest absorbance is used for endpoint detection. However, when the absorbance response exceeds the desired response, it is preferable to use the wavelength of the secondary absorption peak instead. If a reduced response to a particular molecule is desired, such as in the case where the concentration of the molecule is such that the maximum absorbance of the dominant absorption peak is extremely high, the sensitivity of the instrument optics may be exceeded. A peak with a lower maximum absorbance will then be used so that a high sample concentration can be measured with higher accuracy at a lower absorbance.

This system configuration may also increase dynamic range because lower concentrations of analyte may be measured using the primary absorption peak and higher concentrations of analyte may be measured using the secondary peak without changing the detector system. In this way, both higher and lower concentrations of analyte can be measured within the scope of the instrument. The system also allows the instrument to use the same detector system for different titrations of the molecule to be measured at different absorption peaks.

In addition, a series of titrant pumps may inject titrant into the sample stream to react with more than one analyte and detect the concentration of multiple analytes simultaneously. A single instrument capable of adding all reagents required to analyze a sample having more than one analyte can perform all tests using a single spectrometer as a detector. In contrast, multiple detectors are often required due to the different spectral responses that indicate that the endpoint of the titration has been reached.

Furthermore, an automatic titration system is provided, comprising: a reaction manifold for mixing a batch sample stream containing an unknown concentration of an analyte with a first titrant; a sample pump for pumping the sample stream into the reaction manifold; a first titrant pump for pumping the first titrant into the reaction manifold to contact the sample stream; a multi-wavelength detector for detecting a first titration endpoint of a reaction between the analyte and the first titrant; and a controller communicatively coupled with the sample pump, the first titrant pump, and the detector, wherein the controller controls the sample pump to set a flow rate of the sample stream, controls the first titrant pump to set a flow rate of the first titrant, and receives data from the detector to detect the first titration endpoint of the reaction between the analyte and the first titrant, and determines an analyte concentration at the first titration endpoint.

The auto-titration system described herein may allow the sample stream to contain two or more analytes.

Additionally, the auto-titration system described herein may further comprise a second titrant pump for pumping a second titrant into the reaction manifold to contact the batch sample flow or the continuous flow and the updated sample flow. The multi-wavelength detector may further detect a second titration endpoint of the reaction between the analyte and the second titrant, the controller further communicatively coupled to the second titrant pump, and the controller further controls the second titrant pump to set a flow rate of the second titrant, and receives data from the detector to detect the second titration endpoint of the reaction between the analyte and the second titrant, and determine the analyte concentration at the second titration endpoint.

The auto-titration system described herein may react the second titrant with the second analyte.

The auto-titration system described herein may further comprise a third titrant pump for pumping a third titrant into the reaction manifold to contact the batch sample flow or the continuous flow and the updated sample flow. The multi-wavelength detector may further detect a third titration endpoint of the reaction between the analyte and the third titrant, the controller further communicatively coupled to the third titrant pump, and the controller further controls the third titrant pump to set a flow rate of the third titrant, and receives data from the detector to detect the third titration endpoint of the reaction between the analyte and the third titrant, and determine the analyte concentration at the third titration endpoint.

The auto-titration system described herein may react a third titrant with a third analyte.

Likewise, the auto-titration system described herein may make the multi-wavelength detector a spectrometer.

The automatic titration system may make the adjusting reagent a pH buffer, a reaction catalyst, a chemical indicator, a chelating agent, a surfactant, a conductivity-altering salt, an ion-pairing reagent, a biochemical substance, or a combination thereof.

The auto-titration system described herein may include a conditioning reagent comprising potassium iodide, sulfuric acid, acetic acid, a starch indicator, ammonium molybdate, or a combination thereof.

The automatic titration system may include a conditioning reagent pump further comprising a first conditioning reagent pump for pumping the first conditioning reagent and a second conditioning reagent pump for pumping the second conditioning reagent.

The automatic titration system can have the first conditioning reagent be a metal iodide and the second conditioning reagent be an indicator.

The auto-titration system described herein may cause the conditioning reagent pump to inject the conditioning reagent into the batch sample stream or the flowing sample stream, wherein the controller is communicatively coupled to the conditioning reagent pump and configured to control the conditioning reagent pump to set a flow rate of the conditioning reagent injected into the continuous flow and the updated sample stream.

Alternatively, described herein is a method for quantifying a target analyte concentration in a batch sample stream, comprising: adding the sample to an analyzer comprising a manifold and a multi-wavelength detector; quantifying the target analyte concentration by adding a titrant to the analyzer, and by changing the titrant concentration by increasing or decreasing the flow rate of the titrant within a specified range to set a titrant concentration change; and detecting a titration endpoint of a reaction between the target analyte and the titrant in the sample stream over a specified target analyte concentration range; wherein the sample stream comprises two or more analytes.

The method may further comprise the sample stream further comprising a second analyte.

The methods described herein may further comprise quantifying the second analyte by continuously adding the second titrant to the batch sample stream or to the continuous flow and continuous update sample stream.

The method may further comprise the sample stream with a third analyte.

The quantification method may further comprise quantifying the third analyte by continuously adding a third titrant to the batch sample stream or the continuously flowing and continuously updating sample stream.

The method may be such that the known flow rate of the sample is from about 1 μl/min to about 200 mL/min.

The method may be such that the known flow rate of the sample is from about 5 mL/min to about 25 mL/min.

The quantification method may further comprise detecting the titration endpoint using a multi-wavelength detector at a defined distance from the titrant addition point, and calculating the titrant concentration using the distance between the detector and the titrant addition point, the flow rate of the titrant, and the system volume.

The methods described herein may further comprise varying the concentration of the titrant by controlling its flow rate, wherein the detector signal from the titrated reaction product correlates in time with the titrant concentration.

The method may further comprise administering a known concentration of calibrator into the sample stream, detecting the concentration of calibrator, and calculating the response.

The method of quantifying may further comprise controlling the titrant concentration using a feedback loop that is responsive to a detector detecting a reaction between the titrant and the target analyte.

The methods described herein, wherein the conditioning reagent treats the sample stream to improve detection of the target analyte.

The methods described herein can allow the conditioning agent to be a pH buffer, a reaction catalyst, a chemical indicator, a chelating agent, a surfactant, a conductivity altering salt, an ion pair agent, a biochemical species, or a combination thereof.

The methods described herein can increase or decrease the flow rate of the continuous flow and continuously updated sample stream depending on whether a titration endpoint can be detected within a specified target analyte concentration range.

Fig. 1 is a schematic diagram of an automatic titrator 100. The controller may control parameters of sample pump 10, first modulating reagent pump 12, second modulating reagent pump 14, third modulating reagent pump 16, fourth modulating reagent pump 18, first three-way valve 22, second three-way valve 24, mixing valve 20, four-way valve 40, first titrant pump 42 in fluid communication with valve 44, second titrant pump 48 in fluid communication with valve 46, and detector 60. The sample flows through the sample pump 10, through the line and through the mixing valve 20 to the first liquid mixer 30. The first conditioning reagent flows through the first conditioning reagent pump 12, through the line and through the mixing valve 20 to the first liquid mixer 30. The second conditioning reagent flows through the second conditioning reagent pump 14, through the line and through the mixing valve 20 to the first liquid mixer 30. The third conditioning reagent flows through the third conditioning reagent pump 16, through the line and through the mixing valve 20 to the first liquid mixer 30. The fourth conditioning reagent flows through the fourth conditioning reagent pump 18, through the line and through the mixing valve 20 to the first liquid mixer 30. Once the sample and the first through fourth conditioning reagents are mixed in the first liquid mixer 30, the mixture of sample and conditioning reagent becomes a conditioned sample and flows through the four-way valve 40, with the titrant added from the first titrant pump 42, the second titrant pump 44, or from both the first titrant pump 42 and the second titrant pump 44. Once the titrant is added to the conditioned sample, a reaction mixture is formed and flows through the second liquid mixer 50 to the detector 60.

Fig. 2 is a schematic diagram of an auto-titrator 200. The controller may control parameters of the variable flow rate sample pump 210, the first modulating reagent pump 236, the second modulating reagent pump 238, the third modulating reagent pump 240, the first selector valve 230, the second selector valve 232, the third selector valve 234, the first three-way valve 244, the mixer valve 242, the first liquid mixer 246, the three-way valve 250, the titrant pump 260, the selector valve 262, the second liquid mixer 270, and the detector 280. The sample flows through sample pump 210, through the line and through mixing valve 242 to first liquid mixer 246. A series of

conditioning reagents

212, 214, 216 are connected to a first selector valve 230 and then to a first reagent pump 236. The second series of

conditioning agents

218, 220, 222 are connected to a second selector valve 232 and then to a second conditioning agent pump 238. The third series of

conditioning agents

224, 226, 228 are connected to a third selector valve 234 and then to a third conditioning agent pump 240. Once the sample and series of conditioning reagents are mixed in the first liquid mixer 246, the mixture of sample and conditioning reagents becomes a conditioned sample and flows through the second three-way valve 250, where the first titrant 264, the second titrant 266, or the third titrant 268 flows through the fourth selector valve 262 and the titrant pump 260 into the sample stream through the second three-way valve 250. The conditioned sample then flows through the second liquid mixer 270 and to the detector 280.

A variety of reagents known for standard titration may be used and sufficient addition of titrant will result in a change in the sample. However, in this continuous mode operation, the determinant of "sufficient addition of titrant" corresponds to the rate of titrant addition and the concentration relative to sample flow (and sample concentration). This is because the sample continues to flow through the system, so fresh sample is continuously fed into the manifold containing the first

liquid mixer

30 or 246, the selector valve 40 or the three-way valve 250, and the second

liquid mixer

50 or 270.

Thus, if the titrant is added too slowly, it will not react sufficiently with the conditioned sample and the conditioned sample may not change. In other words, a certain amount of sample will flow through a particular point in the system in a given time. To achieve the desired change, then, a suitable volume of titrant is required to flow through this point at the same time, which corresponds to a sufficient flow rate.

The process may be automated by a controller, such as a Programmable Logic Controller (PLC), using a feedback mechanism from the detector.

The flow rate of the titrant may be varied in a non-linearly varying amount over time. For example, an exponential increase in flow rate will begin with a small change in flow rate while the concentrations involved are small. As the concentration becomes larger over time (because the flow rate continues to increase), small changes in flow rate become less precise than existing concentrations, and the flow rate may increase by a larger amount.

Low concentration analytes can be accurately resolved by small changes in concentration early in the process, while high concentration analytes can be titrated in a shorter time, as the rate of addition of titrant increases more rapidly over time.

For example, low concentrations of peroxide and peracid can be accurately resolved by small changes in concentration early in the process, while high concentrations of peracid and/or peroxide can be titrated in a shorter time, as the rate of addition of titrant increases more rapidly over time.

The advantage of this method is that the analysis of each injection point can be done very quickly by means of sufficiently fast optics. Thus, only a small amount of titrant needs to be added at each point to determine if the flow rate is sufficient to complete a complete titration, and only a small amount of titrant is needed to determine the endpoint. This process may be automated by a device (e.g., a PLC) in a similar manner as described in the alternatives, wherein the controller may control the flow rates of the sample and titrant, detect the titration by means of optical means, and calculate the concentration from the flow rates. In this embodiment, the controller performs the additional task of determining the "cut-off" point above which titration occurs and below which no titration occurs.

A method for quantifying a target analyte concentration in a sample stream comprising: continuously flowing and continuously updating the sample stream at a variable flow rate through an analyzer comprising a manifold and a multi-wavelength detector; quantifying the target analyte concentration by continuously adding a titrant to the analyzer, and by changing the titrant concentration by increasing or decreasing the flow rate of the titrant within a specified range to set a titrant concentration change; and detecting a titration endpoint of the reaction between the target analyte and the titrant over a specified target analyte concentration range.

The methods described herein may further comprise a second titrant flow stream, wherein the titrant concentration in the second titrant flow stream is different from the titrant concentration in the first titrant flow stream.

The methods described herein can provide a variable flow rate of the sample of from about 0.1 μl/min to about 1 mL/min. The methods described herein can provide a variable flow rate of the sample of about 0.1 to about 0.75 mL/min, about 0.1 to about 0.5 mL/min, about 0.1 to about 0.25 mL/min, about 0.1 to about 0.1 mL/min, about 0.1 to about 75 mL/min, about 0.1 to about 50 mL/min, about 0.1 to about 25 mL/min, about 0.1 to about 10 mL/min, about 1 to about 1 mL/min, about 1 to about 0.75 mL/min, about 1 to about 1 mL/min, about 1 to about 25 mL/min, about 1 to about 0.1 mL/min, about 1 μL/min to about 75 μL/min, about 1 μL/min to about 50 μL/min, about 1 μL/min to about 25 μL/min, about 1 μL/min to about 10 μL/min, about 5 μL/min to about 1 mL/min, about 5 μL/min to about 0.75 mL/min, about 5 μL/min to about 1 mL/min, about 5 μL/min to about 25 mL/min, about 5 μL/min to about 0.1 mL/min, about 5 μL/min to about 75 μL/min, about 5 μL/min to about 50 μL/min, about 5 μL/min to about 25 μL/min, or about 5 μL/min to about 10 μL/min.

The methods described herein can provide for variable flow rates of the sample from about 1 mL/min to about 200 mL/min.

The methods described herein can provide a variable flow rate of the sample of about 1 mL/min to about 175 mL/min, about 1 mL/min to about 150 mL/min, about 1 mL/min to about 125 mL/min, about 1 mL/min to about 100 mL/min, about 1 mL/min to about 75 mL/min, about 1 mL/min to about 50 mL/min, about 1 mL/min to about 30 mL/min, about 2 mL/min to about 200 mL/min, about 2 mL/min to about 175 mL/min, about 2 mL/min to about 150 mL/min, about 2 mL/min to about 125 mL/min, about 2 mL/min to about 100 mL/min, about 2 mL/min to about 75 mL/min, about 2 mL/min to about 50 mL/min, about 2 mL/min to about 30 mL/min, about 5 mL/min to about 200 mL/min, about 5 mL/min to about 175 mL/min, about 5 mL/min to about 150 mL/min, about 5 mL/min to about 5 mL/min, about 5 mL/min to about 5 min, about 5 mL/min to about 100 mL/min.

The methods described herein can provide a variable flow rate of the sample of about 200 mL/min to about 100L/min. The methods described herein can provide a variable flow rate of the sample of about 200 mL/min to about 75L/min, about 200 mL/min to about 50L/min, about 200 mL/min to about 25L/min, about 200 mL/min to about 10L/min, about 200 mL/min to about 5L/min, about 200 mL/min to about 2L/min, about 200 mL/min to about 1L/min, about 500 mL/min to about 100L/min, about 500 mL/min to about 75L/min, about 500 mL/min to about 50L/min, about 500 mL/min to about 25L/min, about 500 mL/min to about 10L/min, about 500 mL/min to about 5L/min, about 500 mL/min to about 2L/min, about 1L/min to about 100L/min, about 1L/min to about 75L/min, about 1L/min to about 50L/min, about 1L/min to about 25L/min, about 1L/min to about 8L/min, or about 1L/min to about 8L/min.

The methods described herein can provide for a detection range of analyte concentrations that is a larger range at lower sample flow rates and a smaller range at higher sample flow rates.

The methods described herein further comprise continuously adding a modulating reagent to the sample stream at a concentration proportional to the target analyte concentration.

The methods described herein further comprise detecting a titration endpoint using a multi-wavelength detector at a defined distance from the titrant addition point, and calculating the titrant concentration using the distance between the detector and the titrant addition point, the flow rate of the titrant, and the system volume.

The methods described herein further comprise varying the concentration of the titrant by controlling its flow rate, wherein the detector signal from the titrated reaction product correlates with the titrant concentration in time.

The methods described herein further comprise administering a known concentration of calibrator into the sample stream, detecting the concentration of calibrator, and calculating the response.

The methods described herein may further comprise using a mathematical function to alter the titrant concentration and determine the endpoint of the titration within a particular target analyte concentration range.

The methods described herein may make the mathematical function a linear function, a step-wise function, a sinusoidal function, a square wave function, an exponential function, or a combination thereof.

The methods described herein further include controlling the titrant concentration using a feedback loop that is responsive to a detector detecting a reaction between the titrant and the target analyte.

The methods described herein may further comprise measuring the titration endpoint using a stepwise titrant concentration change over a specified target analyte concentration range.

The methods described herein may allow conditioning reagents to treat a sample stream to improve detection of a target analyte.

The methods described herein can improve detection of target analytes by improving the sensitivity of the detection method.

The methods described herein can allow the conditioning agent to be a pH buffer, an acid, a reaction catalyst, a chemical indicator, a chelating agent, a surfactant, a conductivity altering salt, an ion pair agent, a biochemical species, or a combination thereof.

The methods described herein may use a light-based detector to detect a titration endpoint.

The endpoint of the titration may be indicated by a detectable change when the target analyte is fully reacted with the titrant. The detectable change may be a spectrophotometric change.

The titration system may be used to select the optimal wavelength for the intended titration application. For example, depending on the type of analyte at the endpoint, the titrant, and the composition of the sample stream, the optimal wavelength to detect the particular chemical formed at the endpoint may be determined.

The light-based detector may be a spectrometer.

The spectrometer may pass light through a fixed optical unit, where the light may be detected by an image sensor.

Alternatively, the spectrometer may reflect light onto the sample and back through the entrance slit where it may be detected by the image sensor.

The methods described herein can include the modulating agent comprising potassium iodide, acetic acid, a starch indicator, a molybdate salt, or a combination thereof.

The methods described herein may comprise continuously flowing a processing solution through an analyzer comprising a manifold and a detector; quantifying the concentration of the target analyte by varying the flow rate and thereby the concentration of the titrant within a specified range; and detecting a titration endpoint of the reaction between the target analyte and the titrant over a specific target analyte concentration range.

Various reagents that can be used as modulating reagents are well known to those of ordinary skill in the art and can be applied to a variety of titration systems.

For the methods described herein, the target analyte may comprise hydrogen peroxide, peracetic acid, performic acid, peroxyoctanoic acid, or a combination thereof. Preferably, the target analyte comprises hydrogen peroxide, a peroxyacid, or a combination thereof.

For the methods described herein, the titrant comprises thiosulfate.

For the methods described herein, the modulating agent comprises potassium iodide, acetic acid, a starch indicator, ammonium molybdate, or a combination thereof.

In each of the methods described herein, the actual target analyte concentration may be detected directly, or the actual target analyte concentration may be calculated by detecting the concentration of the reaction product of the target analyte and the titrant.

The process allows it to be implemented anywhere, such as at a processing facility or other sampling point in an industrial or commercial setting that is not conducive to periodic performance of standard titration.

Furthermore, the whole process can be completed in a short time; about 2 minutes 40 seconds. The number can be determined in a shorter time before flushing and preparing the system for another measurement; about 1 minute and 20 seconds.

The methods described herein may further comprise a calibration step. The calibration step may be performed online to calibrate flow rates, measurements, etc. Calibration may be performed prior to each titration to improve the accuracy of the measurement. The calibration may be performed after a predetermined number of measurements or may be prompted by the user. On-line calibration can be performed without significantly slowing down the analysis procedure. Such calibration may include injecting a sample of known concentration and confirming that the system accurately measured the concentration. Measurement is inaccurate to a certain extent; the system can self-adjust to accurately measure a sample of known concentration.

Alternatively, a transparent signal may be emitted once the optical sensor senses any radiation from the light source. Such a system may be used if the color change is sufficiently pronounced, blue-black to transparent as described above. However, it should be noted that such a distinct color change may not be necessary in order for the optical device to be able to accurately detect the titration endpoint with the use of suitable optical equipment. Not all reagents are necessary. For example, the starch indicator may be omitted in the case where certain optics are included in the optical device.

As used herein, "amount" refers to a generally measurable amount, such as mass, concentration, volume, and the like.

Having described the invention in detail, it will be apparent that modifications and variations are possible without departing from the scope of the invention defined in the appended claims.

Examples

The following non-limiting examples are provided to further illustrate the invention.

The caustic-containing samples were titrated using a 0.1N HCl solution as the titrant using the Ecolab alkalinity test kit # 301. The operator measures the endpoint as 10 drops. The spectra are shown in fig. 3A and 3B.

The sharp inflection point at 10 drops in fig. 3B indicates that the titration endpoint was measured by a multi-wavelength detector, such as the bingo (Hamamatsu) C12666 MA.

The pinus C12666MA was interfaced to a laboratory prototype rapid flow titrator and used to monitor the titration endpoint by collecting spectra at each of the test concentrations of 6-40ppm on a sample of approximately 15ppm peracid.

The light from the LED source passes through the sample stream of the fast flow titrator immediately downstream of the Banner sensor module. The spectra are shown in fig. 4A, and the absorbance at each wavelength is calculated from the sample, reference, and dark signals using the following equations and shown in fig. 4B.

It was observed that as the test concentration increased, the measured absorbance decreased. This is the measured transition of the blue starch-triiodide complex to a clear solution at the end point where the triiodide has been completely reduced to iodide (titration end point).

The detectors currently employed in two Yikang automatic titrators use detectors that measure light at 680 nm. The above spectra show that the optimal wavelength for analysis is about 550nm. The absorbance data at 550 and 680nm collected by C12666MA was then compared to the titration results measured by the banna sensor.

The results in fig. 5 show the same trend of absorbance versus concentration curve. The fact that the absorbance values are not the same is due to the following facts: neither optical system is optimized to minimize stray light. Stray light will introduce non-linearities into the absorbance measurement.

The pinus C12666MA is just one example of an array spectrometer that can be used to collect spectroscopic data during titration using the mentioned instrument.

The linearity of the C12666MA response was verified by comparing the absorbance collected by C12666MA with the authentication standard. The spectra of HACH DR/inspection standards in fig. 6 were collected using C12666 MA.

The absorbance was then calculated as described above.

The absorbance of the sample is then compared to the certified absorbance at the wavelength disclosed.

A Radio Shack 276-0320 white LED was used as the light source in this experiment. Note that the deviation was less than 6%, indicating a strong agreement between the authentication standard and the data collected using C12666 MA. As described above, if the optical configuration is optimized, the response can be improved.

These data show that a micro spectrometer is a viable detector system for an auto-titrator system. The use of a micro spectrometer can then enable titration with an endpoint transition not at 680nm to be measured with a single broadband detector.

The pinus massoniana C12666MA was used to monitor spectral changes because several iconic field test kits were used to titrate samples. The samples described above were set up for these titrations. Hardness test kit #307 was used to titrate laboratory 17 grain water. The sample was titrated manually and then titrated within the optical test system. The spectra and drop-wise response of the test are shown in fig. 7A and 7B.

The results of the operation of the two peaks 525 and 620 show an inflection point at 17 drops, which is the end point of the operator measurement.

When introducing elements of the present invention or the preferred embodiments(s) thereof, the articles "a/an" and "the/an" are intended to mean that there are one or more of the elements. The terms "comprising," "including," and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements.

In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.

As various changes could be made in the method without departing from the scope of the invention, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

Claims

1. An automatic titration system, comprising:

a reaction manifold comprising a second liquid mixer in fluid communication with a sample source and a titrant source for mixing a continuous flow and a renewed sample stream containing an unknown concentration of a first analyte with a first titrant and mixing the sample stream containing an unknown concentration of a second analyte with a second titrant;

A sample pump in continuous fluid communication with a sample source and the reaction manifold for pumping the sample stream from the sample source into the reaction manifold through a sample flow inlet;

a first titrant pump in fluid communication with a first titrant source and the reaction manifold for pumping the first titrant into the reaction manifold through a first titrant inlet to contact the continuous flow and the renewed sample stream;

a second titrant pump in fluid communication with a second titrant source and the reaction manifold for pumping the second titrant into the reaction manifold through a second titrant inlet to contact the continuous flow and the renewed sample stream;

a multi-wavelength detector in fluid communication with the reaction manifold for detecting a first titration endpoint of a reaction between the first analyte and the first titrant and for detecting a second titration endpoint of a reaction between the second analyte and the second titrant, wherein the multi-wavelength detector is located downstream of and a defined distance from the first titrant inlet and the second titrant inlet; and

A controller communicatively coupled to the sample pump, the first titrant pump, the second titrant pump, and the multi-wavelength detector,

wherein the auto-titration system further comprises a conditioning manifold comprising a first liquid mixer and downstream of the sample flow inlet, the first and second titrant inlets downstream of the conditioning manifold and upstream of a second liquid mixer, and the second liquid mixer is upstream of the multi-wavelength detector,

wherein the controller controls the sample pump to set a continuous flow rate of the sample stream, controls the first titrant pump to set a continuous flow rate of the first titrant, controls the second titrant pump to set a continuous flow rate of the second titrant, and receives data from the multi-wavelength detector to detect the first titration endpoint of the reaction between the first analyte and the first titrant and to determine a first analyte concentration at the first titration endpoint, and to detect the second titration endpoint of the reaction between the second analyte and the second titrant and to determine a second analyte concentration at the second titration endpoint.

2. The automatic titration system of claim 1, wherein the multi-wavelength detector is capable of detecting signals in the ultraviolet to visible range.

3. The automatic titration system of claim 2, wherein the multi-wavelength detector is a spectrometer.

4. The auto-titration system of claim 1, wherein the reaction manifold further comprises a four-way valve at the first titrant inlet and the second titrant inlet, the four-way valve downstream of the conditioning manifold and upstream of the second liquid mixer.

5. The auto-titration system of claim 4, wherein the conditioning manifold further comprises a valve at the conditioning reagent inlet upstream of the first liquid mixer, and the first liquid mixer is upstream of the first and second titrant inlets.

6. The auto-titration system of claim 1, further comprising a conditioning reagent source in fluid communication with a conditioning reagent pump and a conditioning manifold for pumping conditioning reagent from the conditioning reagent source into the conditioning manifold for mixing with the sample stream.

7. The automatic titration system of claim 6, wherein the conditioning reagent source comprises a pH buffer, a reaction catalyst, a chemical indicator, a chelating agent, a surfactant, a conductivity altering salt, an ion pair reagent, a biochemical species, or a combination thereof.

8. The automatic titration system of claim 7, wherein the conditioning reagent source comprises potassium iodide, sulfuric acid, acetic acid, a starch indicator, ammonium molybdate, or a combination thereof.

9. The automatic titration system of claim 8, wherein the conditioning reagent pump further comprises a first conditioning reagent pump for pumping a first conditioning reagent and a second conditioning reagent pump for pumping a second conditioning reagent, the first conditioning reagent pump in fluid communication with a first conditioning reagent source and the conditioning manifold, the second conditioning reagent pump in fluid communication with the conditioning manifold and a second conditioning reagent source, wherein the first conditioning reagent is a metal iodide and the second conditioning reagent is an indicator.

10. The auto-titration system of claim 6, wherein the controller is communicatively coupled to the conditioning reagent pump and configured to control the conditioning reagent pump to set a flow rate of the conditioning reagent injected into the sample stream.

11. The auto-titration system of claim 1, wherein the first and second titrant inlets are at the same point in the reaction manifold.

12. The auto-titration system of claim 1, wherein the sample stream flows from the sample source through the sample pump, through the sample flow inlet into the reaction manifold, through the reaction manifold, and into the multi-wavelength detector.

13. A method for quantifying a target analyte concentration in a sample stream, comprising:

continuously flowing and continuously updating the sample stream at a known flow rate through an analyzer comprising a manifold and a multi-wavelength detector;

quantifying a first target analyte concentration by continuously adding a first titrant to the analyzer, and setting the first titrant concentration change by changing the first titrant concentration by increasing or decreasing the flow rate of the first titrant within a specified range; and

quantifying a second target analyte concentration by continuously adding a second titrant to the analyzer, and setting the second titrant concentration change by changing the second titrant concentration by increasing or decreasing the flow rate of the second titrant within a specified range;

detecting a first titration endpoint for a reaction between the first target analyte and the first titrant in the sample stream over a specified first target analyte concentration range; and

A second titration endpoint for a reaction between the second target analyte and the second titrant in the sample stream is detected over a specified second target analyte concentration range.

14. The method of claim 13, wherein the sample stream further comprises a third analyte, and

the method further comprises quantifying the third analyte by continuously adding a third titrant to the analyzer and setting the third titrant concentration change by increasing or decreasing the flow rate of the third titrant over a specified range to change the third titrant concentration; and

a third titration endpoint for the reaction between the third target analyte in the sample stream and the third titrant is detected within a specified third target analyte concentration range.

15. The method as in claim 14, further comprising: the first, second or third titration endpoint is detected using the multi-wavelength detector at a defined distance from a first, second or third titrant addition point, and the first, second or third titrant concentration is calculated using a distance between the multi-wavelength detector and the first, second or third titrant addition point, a flow rate and a system volume of the first, second or third titrant.

16. The method of claim 14, further comprising varying the concentration of the first, second, or third titrant by controlling the flow rate thereof, wherein a multi-wavelength detector signal from the titrated reaction product is correlated in time with the first, second, or third titrant concentration.